Article abstract
Nature Structural & Molecular Biology 14, 519 - 526 (2007)
Published online: 7 May 2007 | doi:10.1038/nsmb1240
Opposing classes of prp8 alleles modulate the transition between the catalytic steps of pre-mRNA splicing
Li Liu1, Charles C Query2 & Maria M Konarska1
Abstract
The spliceosome is thought to undergo a conformational change between the two catalytic steps of precursor messenger RNA splicing, although the specific events in this transition are poorly understood. We previously proposed a two-state model of splicing in which the conformations required for the first and second steps are in competition. Here, we identify and characterize a class of prp8 mutants that suppress first-step splicing defects and oppose the action of the previously described prp8 suppressors of second-step defects; these opposing effects parallel those of ribosomal 'ram' and 'restrictive' mutants, which alter fidelity of transfer RNA decoding. On the basis of genetic interactions, we propose that prp8-mediated substrate repositioning during the transition occurs between catalytic-center opening and closure mediated by the U6 small nuclear RNA and the DExH/D ATPase gene prp16. Modulation of these events alters splice-site selection and splicing fidelity.
- The Rockefeller University, New York, New York 10021, USA.
- Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Correspondence to: Maria M Konarska1 e-mail: konarsk@mail.rockefeller.edu
Correspondence to: Charles C Query2 e-mail: query@aecom.yu.edu
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